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Anaerobic function of CNS white matter declines with age

This study was supported by the University of Washington Neurosurgery Training Grant, NIH NS15589 (BRR), and the Sidney Gift Fund.

Margaret A Hamner1, Thomas Möller2 and Bruce R Ransom1,2

  1. 1Department of Physiology and Biophysics, School of Medicine, University of Washington, Seattle, Washington, USA
  2. 2Department of Neurology, School of Medicine, University of Washington, Seattle, Washington, USA

Correspondence: BR Ransom, Department of Neurology, Box no. 356465, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA. E-mail:

Received 16 August 2010; Revised 14 October 2010; Accepted 16 October 2010; Published online 22 December 2010.


The mammalian central nervous system (CNS) is generally believed to be completely dependent on the presence of oxygen (O2) to maintain energy levels necessary for excitability. However, previous studies on CNS white matter (WM) have shown that a large subset of CNS-myelinated axons of mice aged 4 to 6 weeks remains excitable in the absence of O2. We investigated whether this surprising WM tolerance to anoxia varied with age. Acutely isolated mouse optic nerve (MON), a purely myelinated WM tract, was studied electrophysiologically. Excitability in the MONs from 1-month-, 4-month-, and 8-month-old mice was assessed quantitatively as the area under the supramaximal compound action potential (CAP). Anoxia-resistant WM function declined with age. After 60 minutes of anoxia, ~23% of the CAP remained in 1-month-old mice, 8% in 4-month-old mice, and ~0 in the 8-month-old group. Our results indicated that although some CNS axons function anaerobically in young adult animals, they lose this ability in later adulthood. This finding may help explain the clinical impression that favorable outcome after stroke and other brain injuries declines with age.